It can be useful to measure the concentration of a preselected biomarker, or analyte, in a body-fluid such as urine. However, depending on the level of hydration of the patient, urine may be relatively dilute or concentrated and this variability in urine dilution can substantially affect the measured analyte concentration, preventing accurate diagnosis. In order to reduce the effect of the variability of urine sample dilution on the measured analyte concentration, the measured analyte concentration can be normalised by the urine dilution factor, which can be determined from its electrical conductivity.
Electrical conductivity, hereafter referred to as conductivity, is a physical property of materials. The conductivity of a particular material is usually temperature dependent and is therefore usually quoted at 25 degrees Celsius. The conductivity of a given material at 25 degrees Celsius will be referred to as the material's temperature corrected conductivity.
The conductance of a given sample of a given material is related to the conductivity of the material by the length and cross sectional area of the material sample. Conductivity is expressed in Siemens/cm. Conductance is expressed in Siemens and is the inverse of resistance.
US 2006/0073606 A1 discloses a urine analyser which determines urine dilution by measuring the level of creatinine (a coloured substance) by optical colorimitry, and corrects an analyte (in this case, albumin, a protein, which is indicative of kidney disease) concentration measurement with the urine dilution factor. However, the apparatus required for measuring creatinine concentration by optical means is cumbersome and expensive. The analyser relies upon a temperature controller having a heater and thermistor, is bulky, power hungry and unsuitable for adapting to a hand held disposable assay device.
WO 2006/087697 A2 discloses a method of measuring urine dilution by measuring the electrical conductivity of the urine sample. The electrical conductivity of urine is known to be related to its dilution. A measured analyte concentration (in this case, thromboxane, which is indicative of heart disease) is then corrected using the measured electrical conductivity. However, electrical conductivity of a sample is known to vary with sample temperature, therefore a temperature dependent error exists in the corrected analyte concentration result.
In a related area it is also known that the hematocrit, or packed cell volume, of a blood sample is related to the electrical conductivity of the sample. The conductivity of blood varies by about 2% per degree Celcius. U.S. Pat. No. 3,648,160 discloses an apparatus which comprises two conductivity cells, each having a pair of electrodes, and analogue signal processing means for correcting a measure of blood sample conductivity using a measure of conductivity of a reference blood plasma which has had the blood cells removed. The disclosure is unsuitable for use in a convenient point of care device, such as a disposable assay device, since its features render it relatively expensive and unsuitable for interfacing to a microprocessor. The disclosed device is also susceptible to errors in temperature compensation if the blood sample and the reference are not maintained at the same temperature as each other. In addition, the performance of the apparatus changes over time requiring repeated calibration against a known standard.